Friday, January 26, 2007


The following eight paragraphs are snipped from a Time magazine article in October 9 2006. It discusses the small differences between us and some of our nearer relatives in the animal kingdom and how all of that difference can’t be explained simply by genetic differences. Several comments by myself are included between brackets and inserted in the text. If any of my asides are completely ignorant of the facts, please comment on the blog where you’ll also find this article.

The illustration is by Tim O'Brien for the Time magazine article.

Even before the human genome was sequenced back in 2000, says biologist Sean
Carroll of the University of Wisconsin, Madison, "it was estimated that humans had 100,000 genes. When we got the genome, the estimate dropped to 25,000. Now we know the overall number is about 22,000, and it might even come down 
to 19,000.”

This shockingly small number made it clear to scientists that genes alone don't dictate the differences between species; the changes, they now know, also depend on molecular switches that
tell genes when and where to turn on and off. “Take the genes involved in creating the hand, the penis and the vertebrae," says Lovejoy. "These share some of the same structural genes. The pelvis is another example. Humans have a radically different pelvis from that of apes. It's like having the blueprints for two different brick houses. The bricks are the same, but the results are very different."

Those molecular switches lie in the noncoding regions of the genome—once known dismissively as junk DNA but lately rechristened the dark matter of the genome. Much of the genome's dark matter is, in fact, junk—the residue of evolutionary events long forgotten and no longer relevant. But a subset of the dark matter known as functional noncoding DNA, comprising some 3% to 4% of the genome and mostly embedded within and around the 
genes, is crucial. "Coding regions are much easier for us to study," 
says Carroll, whose new book, The Making of the Fittest: DNA and
the Ultimate Forensic Record of Evolution, delves deep into the issue. "But it may be the dark matter that governs a lot of what we 
actually see.”

What causes changes in both the dark matter and the genes themselves as one species evolves into another is random mutation, 
in which individual base pairs—the "letters" of the genetic alphabet—are flipped around like a typographical error. These changes stem from errors that occur during sexual reproduction, as DNA is copied and recombined. Sometimes long strings of letters are duplicated, creating multiple copies in the offspring. Sometimes they're deleted altogether or even picked up, turned around and reinserted backward. [Man—isn’t all this sex talk exciting—turning around and reinserting.] A group led by geneticist Stephen Scherer of the Hospital for Sick Children in Toronto has identified 1,576 apparent
inversions between the chimp and human genomes; more than
half occurred sometime during human evolution. [Reading this Time magazine article, believe it or not, I got a whole new feel for what fucking is all about. Dawkins, in the selfish gene also tells us about how these bits of DNA are arranged and rearranged in the combining activities of replication. He even goes so far—I think I did put this in another blog entry some time back—as to suggest that genes aren’t so easily defined or “separated” one from the other because of these long strands of “dark” matter.]

When an inversion, deletion or duplication occurs in an unused portion of the genome, nothing much changes—and indeed, the human, chimp, and other genomes are full of such inert stretches of DNA. When it happens in a gene or in a functional 
noncoding stretch, by contrast an inversion or a duplication is often harmful. But sometimes, purely by chance, the change gives the new organism some sort of advantage that enables it to produce more offspring, thus perpetuating the change in another generation. [But sometimes, even though a generation or so might have increased progeny, I’ll bet whole ecosystems may have been destroyed and entire lines of successful change destroyed. In millions of years how often did catastrophes like that occur?]

A striking example of how gene dupication may have helped propel us away from our apelike origins appeared in Science last month. A research team led by James Sikela of the University of Colorado at Denver and Health Sciences Center, in Aurora, Colo., looked at a gene that is believed to code for a piece of protein, called DUF1220, found in areas of the brain associated 
with higher cognitive function. The gene comes in multiple copies in a wide range of primates—but, the scientists found, humans carry the most copies. African great apes have substantially fewer copies, and the number found in more distant kin—orangutans and Old World monkeys—drops off even more.

Another discovery, first published online by Nature two months ago, describes a gene that appears to play a role in human
brain development. A team led by biostatistician Katherine Pollard, now at the University of California, Davis, and Sofie Salama, of U.C. Santa Cruz., used a sophisticated computer program to search the genomes of humans, chimps and other vertebrates for
segments that have undergone changes at substantially accelerateded rates. They eventually homed in on 49 discrete areas they dubbed human accelerated regions, or HARs.

The region that changed most dramatically from chimps to humans, known as HARl, turns out to be part of a gene that is active in fetal brain tissue only between the seventh and 19th weeks of gestation. Although the gene's precise function is unknown, that happens to be the period when a protein called reelin helps the human cerebral cortex develop its characteristic six-layer structure. [It’s this layering, if I understand it correctly, that has allowed humans to slowly use language more and more abstractly and for the representations of the brain modules that recognize and combine bits of the material world to escape strict representational functions and to begin to combine the segments of the material world in symbolic relations and to apprehend non-material mental constructs like “future” and “past” and, O, so many more intellectual concepts.] What makes the team's research especially intriguing is that all but two of the HARs lie in those enigmatic functional noncoding regions of the genome, supporting the idea that much of
the difference between species happens there.


Dr. Andras J. Pellionisz said...

For an extensive background, see

A collection of "junk DNA diseases" is found at

CopperKettle said...

About Reelin: its expression is lowered in schizophrenic patients - especially in the upper cortical layers (probably through an epigenetic mechanism - high DNA Methyltransferase activity). (Look in a Wikipedia article on Reelin)